title: Association of TLR2, TLR3, TLR4 and CD14 genes polymorphisms with oral cancer risk and survival.
abstract: OBJECTIVE
  The aim of this study is to investigate association between polymorphisms in TLR2, TLR3, TLR4 and CD14 genes or their haplotypes with oral squamous cell carcinomas (OSCC) risk and survival.
  
  
  METHODS
  The study was conducted on 93 OSCC patients and 104 cancer-free controls. Polymorphisms were genotyped by real-time PCR or PCR-RFLP method.
  
  
  RESULTS
  Significant increase in oral cancer risk was observed in individuals with mutated genotype of TLR3 rs3775291 polymorphism (OR = 1.096, P = 0.036) compared to wild-type. The heterozygous and mutated genotype of TLR3 rs5743312 polymorphism had worse survival in group of patients with stage III tumours (P = 0.043). Multivariate Cox regression analysis revealed that TLR3 rs5743312 polymorphism could be considered as prognostic marker in advanced III stage OSCC (HR = 2.456, P = 0.007), but not independently of nodal status. TLR3 rs3775291 and rs5743312 polymorphisms were in strong linkage disequilibrium. Haplotype TG was associated with worse prognosis in OSCC patients in comparison with common CG haplotype (HR = 1.717, P = 0.042). Interaction among polymorphisms in TLR2, TLR3 and CD14 genes was observed (P = 0.010).
  
  
  CONCLUSIONS
  TLR3 rs5743312 polymorphism could be considered as potential predictor of worse overall survival in advanced oral cancer, but not independently of nodal status. Haplotypes in TLR3 gene might be associated with poor prognosis in OSCC patients.
authors.affiliation: Institute for Medical Research, Military Medical Academy, Belgrade, Serbia; Faculty of Biology, University of Belgrade, Belgrade, Serbia.
authors.forename: K
authors.initials: K
authors.lastname: Zeljic
authors.forename: G
authors.initials: G
authors.lastname: Supic
authors.forename: N
authors.initials: N
authors.lastname: Jovic
authors.forename: R
authors.initials: R
authors.lastname: Kozomara
authors.forename: M
authors.initials: M
authors.lastname: Brankovic-Magic
authors.forename: M
authors.initials: M
authors.lastname: Obrenovic
authors.forename: Z
authors.initials: Z
authors.lastname: Magic
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D015996:Survival Rate; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051196:Toll-Like Receptor 3 / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics
chemical_list: D018950:Lipopolysaccharide Receptors; C495342:TLR2 protein, human; C495344:TLR3 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4
keywords: CD14; TLR; haplotypes; oral cancer risk; overall survival; single-nucleotide polymorphisms